Structural and kinetic insights into flavin-containing monooxygenase and calponin-homology domains in human MICAL3
| Autor: | Haemin Lee, Junsoo Kim, Jonghyeon Son, Yong Kwon Lee, Hyun Suk Jung, Donghyuk Shin, Kyunghwan Kim, Junga Park, Minseo Kim, Han-ul Kim, Seong Yun Hwang, Yeon Jin Roh, Sorah Kim, Kwang Yeon Hwang, Aro Lee, Byung Cheon Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
actin depolymerization Flavoprotein Flavin-containing monooxygenase Calponin homology domain monooxygenases Biochemistry 03 medical and health sciences Protein structure enzyme mechanisms Oxidoreductase calponin-homology domain mical General Materials Science refinement protein structure Cytoskeleton Actin x-ray crystallography 030304 developmental biology chemistry.chemical_classification 0303 health sciences Crystallography biology Chemistry 030302 biochemistry & molecular biology General Chemistry Monooxygenase Condensed Matter Physics Research Papers structure determination QD901-999 biology.protein f-actin |
| Zdroj: | IUCrJ, Vol 7, Iss 1, Pp 90-99 (2020) IUCrJ |
| ISSN: | 2052-2525 |
| Popis: | The structure of human MICAL3 provides information about its mechanism. MICAL is an oxidoreductase that participates in cytoskeleton reorganization via actin disassembly in the presence of NADPH. Although three MICALs (MICAL1, MICAL2 and MICAL3) have been identified in mammals, only the structure of mouse MICAL1 has been reported. Here, the first crystal structure of human MICAL3, which contains the flavin-containing monooxygenase (FMO) and calponin-homology (CH) domains, is reported. MICAL3 has an FAD/NADP-binding Rossmann-fold domain for monooxygenase activity like MICAL1. The FMO and CH domains of both MICAL3 and MICAL1 are highly similar in structure, but superimposition of the two structures shows a different relative position of the CH domain in the asymmetric unit. Based on kinetic analyses, the catalytic efficiency of MICAL3 dramatically increased on adding F-actin only when the CH domain was available. However, this did not occur when two residues, Glu213 and Arg530, were mutated in the FMO and CH domains, respectively. Overall, MICAL3 is structurally highly similar to MICAL1, which suggests that they may adopt the same catalytic mechanism, but the difference in the relative position of the CH domain produces a difference in F-actin substrate specificity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|